title: Amino acid composition of proteins reduces deleterious impact of mutations.
abstract: The evolutionary origin of amino acid occurrence frequencies in proteins (composition) is not yet fully understood. We suggest that protein composition works alongside the genetic code to minimize impact of mutations on protein structure. First, we propose a novel method for estimating thermodynamic stability of proteins whose sequence is constrained to a fixed composition. Second, we quantify the average deleterious impact of substituting one amino acid with another. Natural proteome compositions are special in at least two ways: 1) Natural compositions do not generate more stable proteins than the average random composition, however, they result in proteins that are less susceptible to damage from mutations. 2) Natural proteome compositions that result in more stable proteins (i.e. those of thermophiles) are also tuned to have a higher tolerance for mutations. This is consistent with the observation that environmental factors selecting for more stable proteins also enhance the deleterious impact of mutations.
authors.affiliation: 1] Kavli Institute for Theoretical Physics, Kohn Hall, University of California, Santa Barbara, CA 93106, USA [2] School of Engineering and Applied Sciences and Kavli Institute for Bionano Science and Technology, Harvard University, Cambridge, Massachusetts 02138, USA [3] Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
authors.forename: Sahand
authors.initials: S
authors.lastname: Hormoz
mesh_terms: D019943:Amino Acid Substitution; D000596:Amino Acids / Q000737:chemistry*; D019143:Evolution, Molecular; D005815:Genetic Code; D006801:Humans; D008958:Models, Molecular; D009154:Mutation / Q000235:genetics*; D011506:Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D020543:Proteome; D013816:Thermodynamics
chemical_list: D000596:Amino Acids; D011506:Proteins; D020543:Proteome